TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7827	23704;23705;23706	chr2:178720163;178720162;178720161	chr2:179584890;179584889;179584888
N2AB	7510	22753;22754;22755	chr2:178720163;178720162;178720161	chr2:179584890;179584889;179584888
N2A	6583	19972;19973;19974	chr2:178720163;178720162;178720161	chr2:179584890;179584889;179584888
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-63
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.3153
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
V/A	rs758655083	-1.585	0.041	N	0.378	0.246	0.404733080969	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/F	None	None	0.773	D	0.568	0.329	0.754833360098	gnomAD-4.0.0	1.59146E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02462E-05

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
V/A	0.1808	likely_benign	0.1243	benign	-1.514	Destabilizing	0.041	N	0.378	neutral	N	0.489324623	None	None	N
V/C	0.7863	likely_pathogenic	0.6998	pathogenic	-0.926	Destabilizing	0.944	D	0.563	neutral	None	None	None	None	N
V/D	0.4275	ambiguous	0.2655	benign	-1.584	Destabilizing	0.324	N	0.583	neutral	N	0.493010164	None	None	N
V/E	0.3209	likely_benign	0.2051	benign	-1.546	Destabilizing	0.116	N	0.547	neutral	None	None	None	None	N
V/F	0.1397	likely_benign	0.1137	benign	-1.073	Destabilizing	0.773	D	0.568	neutral	D	0.52320791	None	None	N
V/G	0.2676	likely_benign	0.1962	benign	-1.869	Destabilizing	0.324	N	0.565	neutral	N	0.493770632	None	None	N
V/H	0.5334	ambiguous	0.4094	ambiguous	-1.442	Destabilizing	0.818	D	0.616	neutral	None	None	None	None	N
V/I	0.0727	likely_benign	0.0705	benign	-0.623	Destabilizing	0.09	N	0.529	neutral	N	0.474819317	None	None	N
V/K	0.444	ambiguous	0.3223	benign	-1.395	Destabilizing	0.241	N	0.559	neutral	None	None	None	None	N
V/L	0.1204	likely_benign	0.1046	benign	-0.623	Destabilizing	0.09	N	0.541	neutral	N	0.494847873	None	None	N
V/M	0.1136	likely_benign	0.0942	benign	-0.431	Destabilizing	0.818	D	0.561	neutral	None	None	None	None	N
V/N	0.2676	likely_benign	0.1744	benign	-1.266	Destabilizing	0.388	N	0.593	neutral	None	None	None	None	N
V/P	0.9504	likely_pathogenic	0.903	pathogenic	-0.886	Destabilizing	0.818	D	0.586	neutral	None	None	None	None	N
V/Q	0.3098	likely_benign	0.2198	benign	-1.382	Destabilizing	0.024	N	0.41	neutral	None	None	None	None	N
V/R	0.3848	ambiguous	0.2783	benign	-0.878	Destabilizing	0.388	N	0.617	neutral	None	None	None	None	N
V/S	0.181	likely_benign	0.1207	benign	-1.76	Destabilizing	0.024	N	0.429	neutral	None	None	None	None	N
V/T	0.1406	likely_benign	0.0932	benign	-1.612	Destabilizing	0.001	N	0.214	neutral	None	None	None	None	N
V/W	0.7642	likely_pathogenic	0.6855	pathogenic	-1.363	Destabilizing	0.981	D	0.65	neutral	None	None	None	None	N
V/Y	0.5024	ambiguous	0.4093	ambiguous	-1.044	Destabilizing	0.818	D	0.57	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.